Decellularized dermis in combination with cultivated keratinocytes in a short- and long-term animal experimental investigation
Decellularized dermis in combination with cultivated keratinocytes in a short- and long-term animal experimental investigation
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DOI：
10.1111/j.1468-3083.2007.02326.x
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发表时间：
2008-01-01
影响因子：
9.2
通讯作者：
Foehn, M.
中科院分区：
文献类型：
--
作者：
Bannasch, H.;Stark, G. B.;Foehn, M.
本实验采用两阶段动物实验研究脱细胞真皮作为烧伤创面真皮替代物的可行性。在初始步骤中，在短期试验（n = 20，14天）中，将由人角质形成细胞和脱细胞真皮组成的体外产生的复合移植物（AlloDerm（R））移植到裸鼠上。随后，在长期猪动物模型（n = 10，6个月）中，用脱细胞真皮（部分用成纤维细胞预孵育）和培养的自体角质形成细胞（作为纤维蛋白胶中的细胞悬浮液）对全层伤口进行组合一步移植。在这两个系列中，通过面积测量法评价了肉眼可见的伤口愈合。组织学研究包括形态学和免疫组化参数。短期研究表明，与对照组（上皮移植物）相比，复合移植物成功整合，伤口收缩减少。长期猪研究显示，在用成纤维细胞预孵育的真皮处理的伤口中，肌成纤维细胞形成和收缩减少。4周后，可以注意到真皮基质的结构完整性下降。脱细胞真皮作为真皮重建和角质形成细胞递送载体的模板的效用被示出。可以显示在猪动物模型中通过自体角质形成细胞纤维蛋白封闭剂悬浮液和脱细胞真皮的单步组合闭合全层伤口。成纤维细胞的掺入导致伤口收缩减少，但不能防止真皮完整性的丧失。工程“皮肤”在6个月内保持活力和稳定。
Decellularized human dermis as a potentially ideal scaffold for dermal substitution in severe burns was examined in a two-staged animal experiment. In an initial step, an in vitro generated composite graft consisting of human keratinocytes and decellularized dermis (AlloDerm (R)) was transplanted onto nude mice in a short-term trial (n = 20, 14 days). Subsequently, a combined one-step grafting of full thickness wounds with both decellularized dermis (in part preincubated with fibroblasts) and cultivated autologous keratinocytes as a cell suspension in fibrin glue was done in a long-term porcine animal model (n = 10, 6 months). In both series, macroscopic wound healing was evaluated by planimetry. Histological investigations included morphological as well as immunohistochemical parameters. The short-term study showed both successful integration of the composite grafts and reduction of wound contraction compared with the control group (epithelial grafts). The long-term porcine study displayed reduced myofibroblast formation and contraction in the wounds that had been treated with fibroblast-preincubated dermis. After 4 weeks, a decline of the structural integrity of the dermal matrix could be noticed.The utility of decellularized dermis as template for both dermal reconstitution and keratinocyte delivery vehicle was shown. The closure of full thickness wounds by a single-step combination of an autologous keratinocyte fibrin sealant suspension and acellular dermis in a pig animal model could be shown. Incorporation of fibroblasts led to reduced wound contraction but could not prevent the loss of dermal integrity. The engineered 'skin' remained viable and stable over a period of 6 months.